Metabolic Perturbations Caused by the Over-Expression of mcr-1 in Escherichia coli

Rapid dissemination of the plasmid-born polymyxin resistance gene mcr-1 poses a critical medical challenge. MCR-1 expression is tightly controlled and imposes a fitness cost on the bacteria. We used growth studies and metabolomics to examine growth and metabolic changes within E. coli TOP10 at 8 and...

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Published in:Frontiers in microbiology 2020-10, Vol.11, p.588658-588658
Main Authors: Liu, Yi-Yun, Zhu, Yan, Wickremasinghe, Hasini, Bergen, Phillip J., Lu, Jing, Zhu, Xiao-Qing, Zhou, Qiao-Li, Azad, Mohammad, Nang, Sue C., Han, Mei-Ling, Lei, Tao, Li, Jian, Liu, Jian-Hua
Format: Article
Language:English
Subjects:
colistin
fitness cost
glycerophospholipids
mcr-1
metabolomics
Microbiology
pentose phosphate pathway
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Summary:Rapid dissemination of the plasmid-born polymyxin resistance gene mcr-1 poses a critical medical challenge. MCR-1 expression is tightly controlled and imposes a fitness cost on the bacteria. We used growth studies and metabolomics to examine growth and metabolic changes within E. coli TOP10 at 8 and 24 h in response to different levels of expression of mcr-1 . Induction of mcr-1 greatly increased expression at 8 h and markedly reduced bacterial growth; membrane disruption and cell lysis were evident at this time. At 24 h, the expression of mcr-1 dramatically declined with restored growth and membrane integrity, indicating regulation of mcr-1 expression in bacteria to maintain membrane homeostasis. Intermediates of peptide and lipid biosynthesis were the most commonly affected metabolites when mcr-1 was overexpressed in E. coli . Cell wall biosynthesis was dramatically affected with the accumulation of lipids including fatty acids, glycerophospholipids and lysophosphatidylethanolamines, especially at 8 h. In contrast, levels of intermediate metabolites of peptides, amino sugars, carbohydrates and nucleotide metabolism and secondary metabolites significantly decreased. Moreover, the over-expression of mcr-1 resulted in a prolonged reduction in intermediates associated with pentose phosphate pathway and pantothenate and CoA biosynthesis. These findings indicate that over-expression of mcr-1 results in global metabolic perturbations that mainly involve disruption to the bacterial membrane, pentose phosphate pathway as well as pantothenate and CoA biosynthesis.
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2020.588658